Notch signaling has been shown to play a key role in cell fate decisions in numerous developmental systems. Using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, we reported the expression of human Notch-1 in CD34+ progenitors. In this study, we evaluated the expression of human Notch-1 and Notch-2 protein by hematopoietic cells. In immunofluoresence study, we detected low amounts of Notch-1 and Notch-2 protein in both CD34+ and CD34+Lin− cells, high amounts in CD14+ monocytes as well as B and T cells, but no expression in CD15+ granulocytes. We further found that an immobilized truncated form of the Notch ligand, Delta-1, induced apoptosis in monocytes in the presence of macrophage colony-stimulating factor (M-CSF), but not granulocyte-macrophage colony-stimulating factor (GM-CSF). The widespread expressions of Notch proteins suggest multiple functions for this receptor during hematopoiesis. These studies further indicate a novel role for Notch in regulating monocyte survival.